Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism

Authors

• Yun Zhou, Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Xue Yu, Department of Data Science, University of Mississippi Medical Center, United States of America.
• Ava Nicely, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Gary Cunningham, Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Chaitanya Challa, Anesthesia, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Kenneth McKinley, Emergency Department, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Robert Nickel, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Andrew Campbell, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Deepika Darbari, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Marshall Summar, Divisions of Genetics, Children's National Hospital, George Washington University of Health Sciences, United States of America.
• Suvankar Majumdar, Hematology, Children's National Hospital, George Washington University of Health Sciences, United States of America. Electronic address: smajumdar@childrensnational.org.

Document Type

Journal Article

Publication Date

8-20-2022

Journal

Molecular genetics and metabolism

Volume

137

Issue

1-2

DOI

10.1016/j.ymgme.2022.08.004

Keywords

Amino acid; Arginine; Citrulline; Nitric oxide; Pain crisis; Sickle

Abstract

Nitric oxide depletion secondary to arginase induced arginine deficiency has been shown to be important in the pathophysiology of vaso-occlusion in sickle cell pain crisis. Our objective of this study was to perform a comprehensive amino acid evaluation during sickle cell pain crisis. In a total of 58 subjects (29 in steady-state sickle cell disease and 29 with sickle cell pain crisis), the amino acids related to nitric oxide pathway was significantly decreased during sickle cell pain crisis compared to steady-state sickle cell disease: arginine (p = 0.001), citrulline (p = 0.012), and ornithine (p = 0.03). In addition, the amino acids related to energy metabolism was significantly decreased during a pain crisis: asparagine (p < 0.001), serine (p = 0.002), histidine (p = 0.017), alanine (p = 0.004), tyrosine (p = 0.012), methionine (p = 0.007), cystine (p = 0.016), isoleucine (p = 0.016) and lysine (p = 0.006). The amino acid related to oxidative stress were significantly higher during a sickle cell pain crisis (glutamic acid (p < 0.001). Furthermore, multivariate analysis with partial least squares-discriminant analysis (PLS-DA) showed that deficiencies of the amino acids arginine, asparagine, citrulline, methionine and alanine were the most important related to sickle cell pain crisis.

APA Citation

Zhou, Yun; Yu, Xue; Nicely, Ava; Cunningham, Gary; Challa, Chaitanya; McKinley, Kenneth; Nickel, Robert; Campbell, Andrew; Darbari, Deepika; Summar, Marshall; and Majumdar, Suvankar, "Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism" (2022). GW Authored Works. Paper 1457.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1457

Department

Pediatrics